The architecture of the endoplasmic reticulum (ER) consists of an intricate network of sheets and tubules, but how these domains are generated remains largely unknown. The reticulons and reticulon-like proteins are needed to shape the ER. Surprisingly, yeast missing all these proteins are viable and have few phenotypes. To better understand the role of ER-shaping proteins we screened for mutations that cause cells that lack the reticulons to grow poorly. We found that cells lacking the reticulons grow poorly if they are also missing a complex of proteins that tethers the ER and mitochondria. Close contacts between the ER and mitochondria are necessary for efficient lipid exchange between these organelles and mitochondrial biogenesis. We found the phospholipid exchange between the ER and mitochondria slows in cells missing the reticulons and the ER-mitochondria tethering complex. These findings suggest that reticulons are necessary to maintain functional ER-mitochondria contacts. The second project is to identify proteins required for lipid droplet formation in the ER. We have begun to visualize the early steps of lipid droplet biogenesis in the ER. We are also investigating the roles of FIT proteins and Seipins in lipid droplet biogenesis. In a third project, we have identified two novel reticulon-like proteins that help shape the ER in yeast and in higher eukaryotes. These proteins play a role in peroxisome biogenesis.